title: Magnetic resonance and fluorescence-protein imaging of the anti-angiogenic and anti-tumor efficacy of selenium in an orthotopic model of human colon cancer.
abstract: Tumor progression and angiogenesis are intimately related. To understand the interrelationship between these two processes, real-time imaging can make a major contribution. In this report, fluorescent protein imaging (FPI) and magnetic resonance imaging (MRI) were utilized to demonstrate the effects of selenium on tumor progression and angiogenesis in an orthotopic model of human colon cancer. GEO (well-differentiated human colon carcinoma) cells transfected with green fluorescent protein (GFP) were implanted orthotopically into the colon of athymic nude mice. Beginning at five days post implantation, whole-body FPI was performed to monitor tumor growth in vivo. Upon successful visualization of tumor growth by FPI, animals were randomly assigned to either a control group or a treatment group. Treatment consisted of daily oral administration of the organoselenium compound, methyl-selenocysteine (MSC; 0.2 mg/day × five weeks). Dynamic contrast-enhanced MRI was performed to examine the change in tumor blood volume following treatment. CD31 immunostaining of tumor sections was also performed to quantify microvessel density (MVD). While T1- and T2-weighted MRI provided adequate contrast and volumetric assessment of GEO tumor growth, GFP imaging allowed for high-throughput visualization of tumor progression in vivo. Selenium treatment resulted in a significant reduction in blood volume and microvessel density of GEO tumors. A significant inhibition of tumor growth was also observed in selenium-treated animals compared to untreated control animals. Together, these results highlight the usefulness of multimodal imaging approaches to demonstrate antitumor and anti-angiogenesis efficacy and the promise of selenium treatment of colon cancer.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. mukund.seshadri@roswell_park.org
authors.forename: Arup
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Steve G
authors.initials: SG
authors.lastname: Turowski
authors.forename: Ivan Dominguez
authors.initials: ID
authors.lastname: San Martin
authors.forename: Ashwani
authors.initials: A
authors.lastname: Rajput
authors.forename: Youcef M
authors.initials: YM
authors.lastname: Rustum
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Mukund
authors.initials: M
authors.lastname: Seshadri
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D049452:Green Fluorescent Proteins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011897:Random Allocation; D017279:Selenocysteine / Q000031:analogs & derivatives; D023041:Xenograft Model Antitumor Assays
chemical_list: D016566:Organoselenium Compounds; D017279:Selenocysteine; D049452:Green Fluorescent Proteins; D003545:Cysteine; C002979:selenomethylselenocysteine